An Overview of In Vitro Release Methods for Long-Acting Injectable Products Based on PLGA.

Long-acting injectables (LAIs) are widely used for chronic conditions such as schizophrenia, opioid use disorder, and HIV. Their prolonged efficacy improves adherence and reduces dosing frequency. Among these systems, poly(lactide-co-glycolide) (PLGA)-based formulations are commonly used to deliver drugs ranging from small molecules to peptides and proteins. In vitro release (IVR) tests play a critical role in evaluating drug product performance for both immediate- and prolonged-release dosage forms. However, there is a lack of standardized compendial IVR methods for the assessment of LAIs. This lack impedes the development of new drug products in this area and also complicates their regulatory approval process. Considering the complexity of drug release mechanisms and the diversity of various formulation design approaches, it is not possible to devise a universal IVR method that is applicable to all LAI products. The in vitro release test applied for quality control should be simple, robust, reproducible, and discriminatory. On the other hand, more complex biorelevant media and methods are often used during development to better reflect physiological conditions. This article provides a comprehensive review of compendial and non-compendial methods used for in vitro release testing of PLGA-based LAIs (microspheres and in situ forming implants), with the goal of aiding the development and standardization of future methodologies.